Invited Speaker

Extended Spectrum of Activity of Forodesine, a Purine Nucleoside Phosphorylase Inhibitor
Anna R.K. Franklin
USA

Forodesine (BCX - 777, immucillin-H) is an inhibitor of purine nucleoside phosphorylase (PNP) that was developed as therapy for T-cell malignancies, particularly T-cell acute lymphoblastic leukemia (T-ALL). PNP inhibitors block deoxyguaniosine (dGuo) degradation leading to the accumulation of dGuo triphosphate, which is toxic to T lymphocytes. However, forodesine has been found to have in vitro activity against chronic lymphocytic leukemia, a B-cell malignancy. We tested forodesine on 10 primary samples of acute leukemia from children and young adults. Eight patients had pre-B acute lymphoblastic leukemia, 1 had T- ALL and 1 had AML. Forodesine induced apoptosis in all of these samples, as well as inhibiting DNA, RNA and protein synthesis. By elucidating the mechanism of action, forodesine can be utilized in therapy for other malignancies as well combined with other therapies in a rational manner